Inhibition of microglial nitric oxide production by hydrocortisone and glucocorticoid precursors

Viral and bacterial infection in the central nervous system can induce nitr ic oxide production, which serves as a major host defense against invading microorganisms. Glucocorticoids secretion is enhanced and immune responses are diminished in stressed animals or in patients suffering depression. Usi ng N9 microglial cells, this study tested the hypothesis that glucocorticoi ds and their precursors caused an impaired immune defense in animals becaus e these compounds could inhibit microglial nitric oxide production. Results indicated that both hydrocortisone and the synthetic glucocorticoid, dexam ethasone, were potent inhibitors of the microglial nitric oxide production. While glucocorticoid precursors were not as potent as hydrocortisone, the potency of these precursors increased linearly as they advanced on the bios ynthesis pathway. Northern and Western blot analyses indicated that hydroco rtisone and dexamethasone might interfere with the inducible nitric oxide s ynthase at either the transcription or at the post-translational level, dep ending on the concentrations used. These results suggest that glucocorticoi ds have the ability to block nitric oxide production by microgila, which co uld partially explain the impaired immune protection against infection in t he central nervous system in stressed animals.